The Structure Basis For TRIM25 Recognizing RIG-Ⅰ

TRIM25 belongs to the tripartite motif(TRIM)family and plays critical roles in cell proliferation,organ development,cancer proliferation,migration and antiviral innate immunity[1].TRIM25 is an E3 liase with RIG-Ⅰ as its substrate for ubiquintination.RIG-Ⅰ is a member of the RLR family and can recognize virual RNA to change its atuoinhibited state to activated state by resleasing the N-terminal tandem CARD domains.TRIM25 interacts with the activated RIG-Ⅰ through its PRYSPRY domain which binds the CARD domains of RIG-Ⅰ for the subsequent ubiquitination by the TRIM25 RING domain conjugated E2-Ubiquitin.After the ubiquitination,RIG-Ⅰ would become oligomeric and interact with MAVS to form a filament structure on mitochondria for activating the antiviral signal pathway and inducing the production of IFN.It is still unkonwn how TRIM25 interacts with RIG-Ⅰ and causing the downstream activation.To answer this question,the structure of PRYSPRY domain of TRIM25 was solved by X-ray crystallography and the NMR chemical shift perturbation experiments in conjunction with cell based assay and computational modeling were empolyed to ravel the mode of interaction between TRIM25 and RIG-Ⅰ.We hypothesized a signal transduction model to explain the dynamic process for RIG-Ⅰ binding to TRIM25 and its ubiquitination,which provides a better understanding on the RIG-Ⅰ antivirus pathway.